The proposed research will focus upon the questton of how tissue cells such as fibroblasts adhere to substrata and how they achieve locomotion by exerting traction against these substrata. By determining the centrifugal force needed to detach cells from various artificial substrata, the strength of cell adhesion will be measured directly and will be compared for a variety of cell types and substrata. It will also be determined whether the preferential movement of cells onto more adhesive substrata results from preferential extension of cell processes onto more adhesive areas or alternatively whether this results from the preferential detachment of those cell processes attached to less adhesive areas of substratum. Combining the method of interference reflection microscopy with micromanipulation and the use of haptotactic substrata it will be determined which of the cell contacts with the substratum are actually adhesions and the sizes, number and distributions of these adhesions will be compared for a vapiety of substrata, which have already been shown to be differentially adhesive to cells. In addition it will be determined whether the actual area of cell-substratum adhesion is actually reduced during mitosis and after treatment with trypsn or E.D.T.A., or alternatively, whether the tips of the retraction fibers of rounded cells actually correspond to the adhesion points formed prior to rounding up. It will also be determined whether the sites of formation of these adhesions can be dictated by patterns of substratum adhesiveness and whether the cells capacity for forming adhesions can be reduced by repeatedly removing the adhering portions of its membrane. In addition the mechanism by which amphibian cells exert traction during gastrulation will be studied by marking the cell surfaces with visible particles or with ferritin, and by inserting flexible plasma clot substrata into the path of the invaginating bottle cells.